Neurosurgery outcomes and complications in a monocentric 7-year patient registry

Introduction Capturing adverse events reliably is paramount for clinical practice and research alike. In the era of “big data”, prospective registries form the basis of clinical research and quality improvement. Research question To present results of long-term implementation of a prospective patient registry, and evaluate the validity of the Clavien-Dindo grade (CDG) to classify complications in neurosurgery. Materials and methods A prospective registry for cranial and spinal neurosurgical procedures was implemented in 2013. The CDG – a complication grading focused on need for unplanned therapeutic intervention – was used to grade complications. We assess construct validity of the CDG. Results Data acquisition integrated into our hospital workflow permitted to include all eligible patients into the registry. We have registered 8226 patients that were treated in 11994 surgeries and 32494 consultations up until December 2020. Similarly, we have captured 1245 complications on 6308 patient discharge forms (20%) since full operational status of the registry. The majority of complications (819/6308 ​= ​13%) were treated without invasive treatment (CDG 1 or CDG 2). At discharge, there was a clear correlation of CDG and the Karnofsky Performance Status (KPS, rho ​= ​-0.29, slope -7 KPS percentage points per increment of CDG) and the length of stay (rho ​= ​0.43, slope 3.2 days per increment of CDG)

A point mutation in cpsE renders Streptococcus pneumoniae nonencapsulated and enhances its growth, adherence and competence.

BACKGROUND: The polysaccharide capsule is a major virulence factor of the important human pathogen Streptococcus pneumoniae. However, S. pneumoniae strains lacking capsule do occur. RESULTS: Here, we report a nasopharyngeal isolate of Streptococcus pneumoniae composed of a mixture of two phenotypes; one encapsulated (serotype 18C) and the other nonencapsulated, determined by serotyping, electron microscopy and fluorescence isothiocyanate dextran exclusion assay.By whole genome sequencing, we demonstrated that the phenotypes differ by a single nucleotide base pair in capsular gene cpsE (C to G change at gene position 1135) predicted to result in amino acid change from arginine to glycine at position 379, located in the cytoplasmic, enzymatically active, region of this transmembrane protein. This SNP is responsible for loss of capsule production as the phenotype is transferred with the capsule operon. The nonencapsulated variant is superior in growth in vitro and is also 117-fold more adherent to and more invasive into Detroit 562 human epithelial cells than the encapsulated variant.Expression of six competence pathway genes and one competence-associated gene was 11 to 34-fold higher in the nonencapsulated variant than the encapsulated and transformation frequency was 3.7-fold greater. CONCLUSIONS: We identified a new single point mutation in capsule gene cpsE of a clinical S. pneumoniae serotype 18C isolate sufficient to cause loss of capsule expression resulting in the co-existence of the encapsulated and nonencapsulated phenotype. The mutation caused phenotypic changes in growth, adherence to epithelial cells and transformability. Mutation in capsule gene cpsE may be a way for S. pneumoniae to lose its capsule and increase its colonization potential

Methodology of calculation of construction and hydrodynamic parameters of a foam layer apparatus for mass-transfer processes

Промислова реалізація методу стабілізації газорідинного шару дозволяє значно розширити галузь застосування пінних апаратів і відкриває нові можливості інтенсифікації технологічних процесів з одночасним створенням маловідходних технологій. У статті встановлені основні параметри, що впливають на гідродинаміку пінних апаратів, розглянуті основні конструкції та режими роботи пінних апаратів. Виявлено зв'язок гідродинамічних параметрів. Розглянуто гідродинамічні закономірності пінного шару. Вказані фактори, що впливають на процес масообміну, як в газовій, так і в рідкій фазах. Проведений аналіз ряду досліджень показав, що перспективним напрямком інтенсифікації процесу масообміну є розробка апаратів з трифазним псевдозрідженим шаром зрошуваної насадки складних форм із сітчастих матеріалів. Отже, необхідне проведення спеціальних досліджень гідродинамічних режимів роботи апарату з сітчастою насадкою і визначенням параметрів, що впливають на швидкість переходу насадки з одного режиму в інший.Industrial implementation of the stabilization method of the gas-liquid layer can significantly expand the field of use of foaming apparatus and opens up new opportunities for intensifying technological processes with the simultaneous creation of low-waste technologies. The article establishes the basic parameters influencing the hydrodynamics of foam apparatus, considers the basic constructions and operating modes of foam apparatus. The connection of hydrodynamic parameters is revealed. The hydrodynamic laws of the foam layer are considered. The indicated factors affecting the process of mass transfer, both in the gas and in the liquid phases. The conducted analysis of a number of studies showed that the perspective direction of intensification of the mass transfer process is the development of apparatuses with a three-phase fluidized bed of an irrigated nozzle of complex forms with mesh materials

Wissensaustausch und Controlling als Schlüsselfaktoren eines adaptiven Waldmanagements

Die sich ändernden klimatischen Bedingungen erfordern Anpassungen der waldbaulichen Strategien. Adaptives Management zielt zum einen darauf ab, Unsicherheiten zu identifizieren und diese durch Managementversuche und Einbezug von Modellierungen zu reduzieren. Zum andern sollen nebst den Hauptentscheidungsträgern bzw. -trägerinnen Akteure von ausserhalb einbezogen werden, um den Wissenspool zu vergrössern. Schliesslich können durch adaptives Management die Zieldefinitionen laufend den sich ändernden Rahmenbedingungen angepasst werden. Ein solches Managementsystem wird in der Literatur als geeignet angesehen, um mit den grossen Unsicherheiten umzugehen. Dabei sind Wissensaustausch und Controlling zentrale Faktoren, die in der Schweizer Waldwirtschaft weiterentwickelt werden können, um die bestehenden Managementstrategien neuen Herausforderungen anzupassen. Eine grosse Herausforderung bei der Umsetzung eines adaptiven Managements sind die langen Zeiträume, welche zwischen der Ausführung von Massnahmen und den Erfolgskontrollen liegen. Für den Wissensaustausch kommt der «Wissens-Filterung» und einer Objektivierung von Wissen eine zentrale Rolle zu: (Neues) Wissen muss bezüglich Relevanz und Verlässlichkeit sorgfältig geprüft und (wenn möglich) verallgemeinert, objektiviert und in den bestehenden Wissenskontext übertragen werden. Als Grundlage für den Lernprozess ist ein effektives Monitoring und Controlling unerlässlich. Auch dabei kommt dem Wissensaustausch zwischen den Beteiligten eine grosse Bedeutung zu. lm Kontext der Schweizerischen Waldwirtschaft sollten sich Fachstellen und Arbeitsgruppen für den Wissensaustausch und die Wissensverbreitung stärker vernetzen. Systeme zur «Filterung» von Wissen sowie für die Kommunikation zwischen Forschung und Praxis können verbessert werden

Axon guidance receptor ROBO3 modulates subtype identity and prognosis via AXL-associated inflammatory network in pancreatic cancer

Metastatic pancreatic cancer (PDAC) has a poor clinical outcome with a 5-year survival rate below 3%. Recent transcriptome profiling of PDAC biopsies has identified 2 clinically distinct subtypes — the “basal-like” (BL) subtype with poor prognosis and therapy resistance compared with the less aggressive and drug-susceptible “classical” (CLA) subtype. However, the mechanistic events and environmental factors that promote the BL subtype identity are not very clear. Using preclinical models, patient-derived xenografts, and FACS-sorted PDAC patient biopsies, we report here that the axon guidance receptor, roundabout guidance receptor 3 (ROBO3), promotes the BL metastatic program via a potentially unique AXL/IL-6/phosphorylated STAT3 (p-STAT3) regulatory axis. RNA-Seq identified a ROBO3-mediated BL-specific gene program, while tyrosine kinase profiling revealed AXL as the key mediator of the p-STAT3 activation. CRISPR/dCas9-based ROBO3 silencing disrupted the AXL/p-STAT3 signaling axis, thereby halting metastasis and enhancing therapy sensitivity. Transcriptome analysis of resected patient tumors revealed that AXLhi neoplastic cells associated with the inflammatory stromal program. Combining AXL inhibitor and chemotherapy substantially restored a CLA phenotypic state and reduced disease aggressiveness. Thus, we conclude that a ROBO3-driven hierarchical network determines the inflammatory and prometastatic programs in a specific PDAC subtype.This work was supported by Max-Eder Research grants of German Cancer Aid to SKS (70112999) and to AN (70113213) and the Wilhelm-Sander-Stiftung (2021.159.1) to SKS. The study was also supported by the DFG grant (KFO 5002) to AN, EH, VE, and SKS and the Volkswagen-Stiftung/Ministry for Culture and Science in Lower Saxony (MWK) to VE (11-25 76251-12-3/16). This work was also supported by the German Ministry of Science and Education (BMBF) project CancerScout (FKZ: 13GW0451A) to HB, SK, and PS. The MD research fellowship of NK was supported by DGVS. The BMBF e:Med program for systems biology (PANC-STRAT consortium, grant no. 01ZX1305C and 01ZX1605C); the Dietmar-Hopp Foundation; the BioRNSpitzen cluster “Molecular- and Cell-based Medicine” and Heidelberger Stiftung Chirurgie supported our work for collecting and processing of patients’ specimens. We thank Stephan A. Hahn (Ruhr University Bochum) for supporting this study with PDX materials. We sincerely thank Waltraut Kopp, Kristina Reutlinger, Eva Schmitt, Dana Wörz, and Dimitra Spyropoulou for their excellent technical support. We thank N.A. Giese, T. Hackert, O. Strobel, and M. Büchler for organizing resected primary PDAC specimens from the EPZ-Biobank and Department of General, Visceral and Transplantation Surgery of the University Hospital Heidelberg